Heterogeneity in Survival Over Time by Age, Sex, and Subsite in Early‐Onset Oral Cavity Cancer

OBJECTIVE: To understand temporal trends in presentation and survival among patients with early-onset oral cavity squamous cell carcinoma (EO-OCSCC). STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database (NCDB), 2004 to 2022. METHODS: Adult patients younger than 50 years diagnosed with OCSCC in the NCDB. Annual case distributions by subsite, sex, and stage were modeled with logistic regression, reporting odds ratios (ORs) per calendar year over time. Kaplan-Meier and Cox proportional hazards analyses assessed 5-year overall survival (OS), stratified by age group, subsite, and stage. RESULTS: Among 178,140 OCSCC cases, 21,630 (12.1%) were EO-OCSCC with median age of 44 years. Tongue was the most common subsite (66.9%) and increased over time (OR/year = 1.03; 95% CI, 1.02-1.04). Female cases rose steadily (OR/year = 1.01; 95% CI, 1.01-1.02), narrowing the male-female gap. Advanced-stage disease increased by 5% annually in tongue tumors and 3% in non-tongue tumors. Five-year OS was higher in tongue (73.7%) than non-tongue tumors (61.5%, P < .001) and improved over time, with annual reductions in mortality risk of 1.1% for tongue and 1.9% for non-tongue tumors. By age group, survival was highest for patients 20-29 years and lowest for those 40-49 years. CONCLUSION: EO-OCSCC is increasingly presenting as tongue primaries and in female patients, with a rising burden of advanced-stage disease. Despite this unfavorable shift, survival has improved modestly across subsites, ages, and stages, underscoring the heterogeneity of EO-OCSCC and the need for earlier detection and awareness.